Abstract
To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.
Highlights
Uveitis refers to a variety of clinical presentations with different phenotypes
Paired sera and aqueous humor (AH) samples obtained from patients with uveitis related to toxoplasmosis (TU) (n = 16), uveitis related to Behcet disease (n = 7) and ocular sarcoidosis (N = 15) served as disease controls
We compared the median AH concentrations of cytokines and chemokines between noninflammatory controls and patients with uveitis related to Behcet disease, sarcoidosis, TU and idiopathic uveitis (Fig 9) for those 4 mediators significantly elevated in idiopathic uveitis as compared as noninflammatory controls: IL-6, TNF-α, IL-12 and IP-10
Summary
Uveitis refers to a variety of clinical presentations with different phenotypes. Idiopathic from unknown etiology (or idiopathic uveitis) is reported for 36% of cases [1, 2], and 10% leads to blindness in developed countries. Some idiopathic uveitis could be autoimmune or infectious uveitis undiagnosed. The idiopathic character is a diagnosis of exclusion when the clinical, radiological and biological work-up are noncontributive and the ophthalmological examination is nonpathognomonic for a particular entity. The question remains: what is the initial cause of those inflammatory process in the eye? Familial cases of intermediate idiopathic uveitis and other autoimmune diseases suggest that genetic variants and/or a single environmental agent are probably the cause of auto-immune diseases. The hypothesis of a susceptibility to uveitis stemming from genetic determinants, as seen in other immunological diseases, has been initially suggested by their mode of hereditary transmission in certain families. One hypothesis would that an infectious agent (virus or bacteria) would activate systematically the autoreactive T lymphocytes in patients genetically predisposed. We know that in certain cases, viral infections even eradicated, may have introduced immune responses, propagate these responses by using molecular mimics
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